AMELIORATION OF ESTABLISHED MURINE COLLAGEN-INDUCED ARTHRITIS WITH ANTI-IL-1 TREATMENT

Inflammatory cytokines have been implicated in the pathogenesis of rhe umatoid arthritis. To validate a key role for IL-1 in arthritic proces ses we have studied the protective effect of neutralizing antimurine I L-1 antibodies in the murine collagen-induced arthritis (CIA) model. C ombination of anti-IL-1 alpha and anti-IL-1 beta given before onset of arthritis was shown to prevent disease completely. Remarkably, a sing le treatment was also highly effective in the established phase of art hritis, reducing both inflammation as well as cartilage destruction. S uppression was most pronounced with the combination, but anti-IL-1 bet a alone also induced significant relief. Finally, we studied the prote ctive effect of IL-1 neutralization on cartilage metabolism in a unila teral expression model of collagen arthritis. To this end zymosan was injected in one knee joint before onset of disease, resulting in accel erated expression in that particular joint and the draining paw. Anti- IL-1 treatment started after accelerated expression of arthritis was a ble to fully normalize chondrocyte synthetic function, which was highl y suppressed in the control group. It is concluded that IL-1 is an imp ortant determinant in both inflammation and cartilage destruction in c ollagen arthritis, and this may have implications for therapy in human arthritis.